Prevention of Bronchopulmonary Dysplasia (BPD)

< Back to Medical care & clinical practice

Authors

Poets C, Zimmermann LJI, Hellström-Westas L, Buonocore G, Hallman M, Lista G, van Kaam A, Kramer B

Click on the image to read the standard in brief.

Target group

Very preterm and particularly extremely preterm infants, intrauterine growth restricted (IUGR) and small-for-gestational-age (SGA) infants, and parents


User group

Healthcare professionals, neonatal units, hospitals, and health services


Statement of standard

Bronchopulmonary Dysplasia (BPD) is best prevented using evidence-based strategies, including continuous distending pressure or non-invasive ventilation to maintain patency of airways and avoiding invasive mechanical ventilation and intermittent hypoxemia when possible, minimally invasive early administration of exogenous surfactant, aiming at volume targeted ventilation and early caffeine, administration of systemic steroids in infants still requiring mechanical ventilation during their 2nd postnatal week, and supporting parental involvement in preterm infant care starting shortly after birth.


Rationale

Bronchopulmonary Dysplasia (BPD) results from the effects of non-physiologic stimuli (e.g. inflammation, ventilator induced lung injury, high supplemental oxygen levels) in an infant with underdeveloped lungs and defence mechanisms (e.g. anti-oxidant capacity). (1) Interventions that reduce inflammation (e.g. steroids) or any of these non-physiologic stimuli (e.g. mechanical ventilation) are likely to reduce BPD rates. Improving patient comfort through the early involvement of parents and/or family-centred care is also associated with a reduction in BPD rates. (2–4) Some of these interventions may additionally promote the survival of the target group; none decreases the chances of survival. (5)

BPD is defined as supplemental oxygen or ventilator requirement at 36 weeks post-menstrual age (PMA). According to one proposal these requirements last for ≥3 consecutive days to maintain arterial oxygen saturation in the 90-95% range plus the presence of persistent parenchymal lung disease. (6) There are proposals for defining the grade of BPD at 36 weeks PMA which differ in their predictive power. (7) BPD is a risk factor for later respiratory hospitalisation in infancy, compromised lung function in childhood, neurodevelopmental impairment, and a potential risk factor for chronic obstructive pulmonary disease in later life. (1,8) However, the risk of BPD has not decreased in population-based studies of extremely preterm infants (9), suggesting that more innovative research is needed to enhance the benefits. 


Benefits

Short-term benefits

Long-term benefits


Components of the standard

Component

Grading of evidence

Indicator of meeting the standard

For parents and family

  1. Parents are informed by healthcare professionals about Bronchopulmonary Dysplasia (BPD) and strategies to minimise its risk. (1)

A (High quality)

Patient information sheet1

  1. Parents are closely involved in their baby’s care, e.g. through family-integration or NIDCAP. (2–4)

A (Moderate quality)

Parent feedback

For healthcare professionals

  1. A unit guideline on the management and prevention of BPD is adhered to by all healthcare professionals, and includes the following advice:

A (High quality)

Guideline

  • Surfactant is administered via a thin intra-tracheal catheter if FiO2 is >0.30 or using INSURE (intubation surfactant and extubation). (19) Some extremely immature infants still require early intubation, ventilation and surfactant.

A (High quality)

Guideline

  • Volume targeted ventilation (at 5-7 ml/kg) is used plus adequate PEEP level, if intubation cannot be avoided. (12)

A (High quality)

Guideline

  • Infants on n-CPAP are switched to synchronised nasal ventilation if respiratory distress visible while on CPAP. (20)

A (High quality)

Guideline

  • Caffeine is administered from day 1-2 after birth (10 mg/kg loading, 5 mg/kg/d maintenance for caffeine base). (13,14)

A (High quality)

Guideline

  • Vitamin A is considered (5000 IE i.m. three times/week for week 1-4 after birth). (15)

A (High quality)

Guideline

  • If mechanical ventilation is still necessary during postnatal week 2, postnatal steroid use is considered (dexamethasone at the lowest effective dose possible). (21,22)

A (High quality)

Guideline

  • In infants receiving additional inspired oxygen, avoiding IH is considered, e.g. through closed-loop oxygen control. (9,17)

A (High quality)

Guideline

  • Breast milk is the preferred nutrient. (18)

A (High quality)

Guideline

  • Efforts to reduce rates of infection, as a risk factor for BPD, are made. (23)

A (High quality)

Guideline

  1. Training on the management and prevention of BPD is attended by all responsible healthcare professionals.

B (High quality)

Training documentation

For neonatal unit

  1. A unit guideline on prevention and management of BPD is available and regularly updated.

B (High quality)

Guideline

  1. A protocol is in place for how to involve parents early on in their baby’s care.

A (Moderate quality)

Clinical records

For hospital

  1. Training on management and prevention of BPD is ensured.

B (High quality)

Training documentation

  1. Institutional BPD rates are monitored together with length of hospital stay and use of supplemental oxygen.

B (High quality)

Audit report2

For health service

  1. A national guideline on management and prevention of BPD is available and regularly updated.

B (High quality)

Guideline


1The indicator ‘patient information sheet’ is an example for written, detailed information, in which digital solutions are included, such as web-based systems, apps, brochures, information leaflets, and booklets.

2The indicator ‘audit report’ can also be defined as a benchmarking report.

Where to go – further development of care

Further development

Grading of evidence

For parents and family

N/A

For healthcare professionals

  • Investigate in larger numbers whether using synchronised nasal ventilation rather than n-CPAP is the preferred mode of nasal respiratory support. (12)

A (Moderate quality)

  • Evaluate alternative anti-inflammatory strategies, e.g. hydrocortisone, inhaled budesonide, or tracheal instillation of budesonide together with exogenous surfactant to generate more data on their long-term effectiveness and safety. (16,24,25)

A (High quality)

  • Investigate the benefits of high frequency oscillatory ventilation for preventing BPD, particularly in infants with significant oxygen requirement and low lung compliance despite surfactant treatment and mechanical ventilation. (12)

A (Moderate quality)

  • Investigate whether high-flow nasal cannula, compared to n-CPAP, can reduce the risk of developing BPD. (26,27)

A (High quality)

  • Investigate the role of eradicating Ureaplasma urealyticum shortly after birth. (28)

A (Moderate quality)

  • Investigate oral Vitamin A administration as well as the role of other nutrients. (15,29)

A (High quality)

  • Find the optimal drug and dose for postnatal steroid treatment.  (15)

A (Moderate quality)

  • Investigate the potential of mesenchymal stem cells in repairing the injured immature lung. (30,31)

A (Moderate Quality)

  • Investigate the effect of various delivery-room practices and of early enteral feeding on the prevention of BPD. (22)  

A (High Quality)

  • Investigate the role of inhaled nitric oxide (NO) in preventing BPD, and of vasodilators, particularly inhaled NO, in the early persistence of pulmonary hypertension, for possible prevention of BPD. (32)

A (Moderate Quality)

  • Investigate the role of serum markers (e.g. Clara cell secretory protein 16 (CC16), KL-6 and end-tidal carbon monoxide) and develop advanced prediction models for the early identification of infants at increased risk of BPD. (33)

A (Moderate Quality)

  • Investigate new management practices during very high-risk perinatal transition; among them antenatal N-acetylcysteine, prophylactic acetaminophen to extremely preterm infants for prevention of BPD. (34,35)

A (Moderate Quality)

  • Investigate towards improving the anti-inflammatory properties of surfactant drugs (36) and the use of surfactant as carrier of other drugs.

A (Moderate Quality)

  • Investigate methods for advancing the perinatal transition of high-risk extremely preterm infants.

A (Moderate Quality)

For neonatal unit

  • Identify further synergies between family-oriented care and advanced neonatal management practices

A (Moderate Quality)

For hospital

  • Encourage multidisciplinary collaboration between perinatal and neonatal teams, as well as neonatal and paediatric teams.

A (Moderate Quality)

For health service

  • Promote research on medicines for very high-risk neonates through legislation similar to medicines for children.

B (Moderate Quality)


Getting started

Initial steps

For parents and family

  • Parents are verbally informed by healthcare professionals about BPD and strategies to minimise its risk. (1)
  • Parents are educated by healthcare professionals about the particular need of a smoke-free environment.

For healthcare professionals

  • Attend training on management and prevention of BPD.
  • Apply exogenous surfactant via less/minimally invasive administration via a thin catheter, i.e. without using an endotracheal tube (LISA or MIST), or via the INSURE method (intubation, surfactant, extubation); under investigation: nebulisation, pharyngeal instillation and laryngeal mask airway (LMA) surfactant administration.
  • Use nasal continuous positive airway pressure (n-CPAP) instead of intubation and mechanical ventilation. (37)
  • Start caffeine on postnatal day 1 or 2 instead of later.

For neonatal unit

  • Develop and implement a unit guideline on management and prevention of BPD.
  • Develop information material about BPD for parents.

For hospital

  • Support healthcare professionals to participate in training on management and prevention of BPD.

For health service

  • Develop and implement a national guideline on management and prevention of BPD.

  1. Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med. 2007 Nov 8;357(19):1946–55.
  2. Peters KL, Rosychuk RJ, Hendson L, Coté JJ, McPherson C, Tyebkhan JM. Improvement of short- and long-term outcomes for very low birth weight infants: Edmonton NIDCAP trial. Pediatrics. 2009 Oct;124(4):1009–20.
  3. Lv B, Gao X ronga, Sun J, Li T tao, Liu Z ye, Zhu L hui, et al. Family-Centered Care Improves Clinical Outcomes of Very-Low-Birth-Weight Infants: A Quasi-Experimental Study. Front Pediatr. 2019 Apr 12;7:138.
  4. Lehtonen L, Lee SK, Kusuda S, Lui K, Norman M, Bassler D, et al. Family Rooms in Neonatal Intensive Care Units and Neonatal Outcomes: An International Survey and Linked Cohort Study. J Pediatr. 2020 Nov;226:112-117.e4.
  5. Poets CF, Lorenz L. Prevention of bronchopulmonary dysplasia in extremely low gestational age neonates: current evidence. Arch Dis Child Fetal Neonatal Ed. 2018 May;103(3):F285–91.
  6. Higgins RD, Jobe AH, Koso-Thomas M, Bancalari E, Viscardi RM, Hartert TV, et al. Bronchopulmonary Dysplasia: Executive Summary of a Workshop. J Pediatr. 2018 Jun;197:300–8.
  7. Vyas-Read S, Logan JW, Cuna AC, Machry J, Leeman KT, Rose RS, et al. A comparison of newer classifications of bronchopulmonary dysplasia: findings from the Children’s Hospitals Neonatal Consortium Severe BPD Group. J Perinatol Off J Calif Perinat Assoc. 2022 Jan;42(1):58–64.
  8. Schmidt B, Asztalos EV, Roberts RS, Robertson CMT, Sauve RS, Whitfield MF, et al. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA. 2003 Mar 5;289(9):1124–9.
  9. Abdo M, Hanbal A, Mostafa Asla M, Ishqair A, Alfar M, Elnaiem W, et al. Automated versus manual oxygen control in preterm infants receiving respiratory support: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2021 Apr 8;1–8.
  10. Aldana-Aguirre JC, Pinto M, Featherstone RM, Kumar M. Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2017 Jan;102(1):F17–23.
  11. Stevens TP, Harrington EW, Blennow M, Soll RF. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003063.
  12. Peng W, Zhu H, Shi H, Liu E. Volume-targeted ventilation is more suitable than pressure-limited ventilation for preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2014 Mar;99(2):F158-165.
  13. Davis PG, Schmidt B, Roberts RS, Doyle LW, Asztalos E, Haslam R, et al. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. J Pediatr. 2010 Mar;156(3):382–7.
  14. Park HW, Lim G, Chung SH, Chung S, Kim KS, Kim SN. Early Caffeine Use in Very Low Birth Weight Infants and Neonatal Outcomes: A Systematic Reviewand Meta-Analysis. J Korean Med Sci. 2015 Dec;30(12):1828–35.
  15. Darlow BA, Graham PJ, Rojas-Reyes MX. Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birth weight infants. Cochrane Database Syst Rev. 2016 Aug 22;(8):CD000501.
  16. Doyle LW, Ehrenkranz RA, Halliday HL. Late (> 7 days) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2014 May 13;(5):CD001145.
  17. Jensen EA, Whyte RK, Schmidt B, Bassler D, Vain NE, Roberts RS. Association Between Intermittent Hypoxemia and Severe Bronchopulmonary Dysplasia in Preterm Infants. Am J Respir Crit Care Med [Internet]. 637653600000000000 [cited 2022 May 6]; Available from: https://www.sciencegate.app/document/10.1164/rccm.202105-1150oc
  18. Villamor-Martínez E, Pierro M, Cavallaro G, Mosca F, Kramer B, Villamor E. Donor Human Milk Protects against Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis. Nutrients. 2018;10(2):238.
  19. Kribs A, Roll C, Göpel W, Wieg C, Groneck P, Laux R, et al. Nonintubated Surfactant Application vs Conventional Therapy in Extremely Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. 2015 Aug;169(8):723–30.
  20. Lemyre B, Davis PG, De Paoli AG, Kirpalani H. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database Syst Rev. 2014 Sep 4;(9):CD003212.
  21. Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB, DART Study Investigators. Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized, controlled trial. Pediatrics. 2006 Jan;117(1):75–83.
  22. Onland W, Offringa M, Jaegere APD, Kaam AH van. Finding the Optimal Postnatal Dexamethasone Regimen for Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Systematic Review of Placebo-Controlled Trials. Pediatrics. 2009 Jan 1;123(1):367–77.
  23. Lapcharoensap W, Kan P, Powers RJ, Shaw GM, Stevenson DK, Gould JB, et al. The Relationship of Nosocomial Infection Reduction to Changes in Neonatal Intensive Care Unit Rates of Bronchopulmonary Dysplasia. J Pediatr. 2017 Jan;180:105-109.e1.
  24. Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet Lond Engl. 2016 Apr 30;387(10030):1827–36.
  25. Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, et al. Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2016 Jan 1;193(1):86–95.
  26. Dumpa V, Bhandari V. Non-Invasive Ventilatory Strategies to Decrease Bronchopulmonary Dysplasia—Where Are We in 2021? Children. 2021 Feb;8(2):132.
  27. de Jesus Brito S, Tsopanoglou SP, Galvão EL, de Deus FA, de Lima VP. Can high-flow nasal cannula reduce the risk of bronchopulmonary dysplasia compared with CPAP in preterm infants? A systematic review and meta-analysis. BMC Pediatr. 2021 Sep 16;21(1):407.
  28. Smith C, Egunsola O, Choonara I, Kotecha S, Jacqz-Aigrain E, Sammons H. Use and safety of azithromycin in neonates: a systematic review. BMJ Open. 2015 Dec;5(12):e008194.
  29. Meyer S, Gortner L, NeoVitaA Trial investigators. Up-date on the NeoVitaA Trial: Obstacles, challenges, perspectives, and local experiences. Wien Med Wochenschr 1946. 2017 Sep;167(11–12):264–70.
  30. O’Reilly M, Thébaud B. Stem Cells for the Prevention of Neonatal Lung Disease. Neonatology. 2015;107:360–4.
  31. Chang YS, Ahn SY, Yoo HS, Sung SI, Choi SJ, Oh WI, et al. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr. 2014 May;164(5):966-972.e6.
  32. Abman SH. Pulmonary Hypertension: The Hidden Danger for Newborns. Neonatology. 2021 Jan 1;118(2):211–7.
  33. Zhang ZQ, Huang XM, Lu H. Early biomarkers as predictors for bronchopulmonary dysplasia in preterm infants: a systematic review. Eur J Pediatr. 2014 Jan 1;173(1):15–23.
  34. Buhimschi CS, Bahtiyar MO, Zhao G, Abdelghany O, Schneider L, Razeq SA, et al. Antenatal N-acetylcysteine to improve outcomes of premature infants with intra-amniotic infection and inflammation (Triple I): randomized clinical trial. Pediatr Res. 2021 Jan;89(1):175–84.
  35. Institut National de la Santé Et de la Recherche Médicale, France. Prophylactic Treatment of the Ductus Arteriosus in Preterm Infants by Acetaminophen [Internet]. clinicaltrials.gov; 2022 Feb [cited 2022 Jun 1]. Report No.: NCT04459117. Available from: https://clinicaltrials.gov/ct2/show/NCT04459117
  36. Airway Therapeutics, Inc. A Phase 1b, Randomized, Blinded, Dose-Determined Study Evaluating the Safety and Tolerability Profile of Intervention With AT-100 (rhSP-D) in Preterm Neonates at High Risk for the Development of Bronchopulmonary Dysplasia (BPD) [Internet]. clinicaltrials.gov; 2022 Apr [cited 2022 Jun 1]. Report No.: NCT04662151. Available from: https://clinicaltrials.gov/ct2/show/NCT04662151
  37. Schmölzer GM, Kumar M, Pichler G, Aziz K, O’Reilly M, Cheung PY. Non-invasive versus invasive respiratory support in preterm infants at birth: systematic review and meta-analysis. BMJ. 2013 Oct 17;347:f5980.

September 2022 / 2nd edition / previous edition reviewed by Hentschel R / next revision: 2025


Recommended citation

EFCNI, Poets C, Zimmermann LJI et al., European Standards of Care for Newborn Health: Prevention of Bronchopulmonary Dysplasia (BPD). 2022.